A formal analysis of cytokine networks in chronic fatigue syndrome.
A formal analysis of cytokine networks in chronic fatigue syndrome.
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DOI：
10.1016/j.bbi.2010.04.012
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发表时间：
2010-10
期刊：
影响因子：
--
通讯作者：
Fletcher MA
中科院分区：
文献类型：
--
作者：
Broderick G;Fuite J;Kreitz A;Vernon SD;Klimas N;Fletcher MA
慢性疲劳综合症(CFS)是一种复杂的疾病，影响着400万美国人，目前还没有确定其特有的损害。我们没有寻找任何单一标志物的缺陷，而是认为CFS与免疫功能调节的严重失衡有关，迫使偏离标准的预编程反应。为了确定这些不平衡，我们应用网络分析在CFS受试者和健康对照组中16种细胞因子的共表达。测定40例女性CFs和59例正常对照血浆中IL-1a、1b、2、4、5、6、8、10、12、13、15、17和23、干扰素-γ、淋巴毒素-α(LT-α)和肿瘤坏死因子-α的浓度。细胞因子共表达网络是根据在每个受试组中发现的成对互信息(MI)模式构建的。这些网络在拓扑上的差异比预期的大得多，CFS网络在设计上更像集线器。局部模块化分析分离出统计上不同的细胞因子群落，可识别为预先编程的免疫功能组件。这表明CFS的Th1和Th17免疫反应高度减弱。Th2标志物的高表达但弱相互作用模式表明已建立的Th2炎症环境。类似地，CFs中关联的改变提供了NK细胞对IL-12和LTα刺激反应减弱的间接证据。这些观察结果与潜伏病毒感染中活跃的几个过程是一致的，仅通过评估标记物的表达是不可能发现的。此外，这项分析确定了可能在恢复正常免疫功能方面靶向的关键亚网络，如IL-2：干扰素γ：肿瘤坏死因子α。
Chronic Fatigue Syndrome (CFS) is a complex illness affecting 4 million Americans for which no characteristic lesion has been identified. Instead of searching for a deficiency in any single marker, we propose that CFS is associated with a profound imbalance in the regulation of immune function forcing a departure from standard preprogrammed responses. To identify these imbalances we apply network analysis to the co-expression of 16 cytokines in CFS subjects and healthy controls. Concentrations of IL-1a, 1b, 2, 4, 5, 6, 8, 10, 12, 13, 15, 17 and 23, IFN-γ, lymphotoxin-α (LT-α) and TNF-α were measured in the plasma of 40 female CFS and 59 case-matched controls. Cytokine co-expression networks were constructed from the pair-wise mutual information (MI) patterns found within each subject group. These networks differed in topology significantly more than expected by chance with the CFS network being more hub-like in design. Analysis of local modularity isolated statistically distinct cytokine communities recognizable as pre-programmed immune functional components. These showed highly attenuated Th1 and Th17 immune responses in CFS. High Th2 marker expression but weak interaction patterns pointed to an established Th2 inflammatory milieu. Similarly, altered associations in CFS provided indirect evidence of diminished NK cell responsiveness to IL-12 and LTα stimulus. These observations are consistent with several processes active in latent viral infection and would not have been uncovered by assessing marker expression alone. Furthermore this analysis identifies key subnetworks such as IL-2:IFNγ:TNFα that might be targeted in restoring normal immune function.
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5.4
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Gu, Yongpeng;Yang, Jianfei;Ouyang, Xinshou;Liu, Weicheng;Li, Hongxing;Yang, Jianjun;Bromberg, Jonathan;Chen, Shu-Hsia;Mayer, Lloyd;Unkeless, Jay C.;Xiong, Huabao
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